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Engineering Photorhabdus luminescens toxin complex (PTC) into a recombinant injection nanomachine.
Life Science Alliance ( IF 3.3 ) Pub Date : 2019-09-20 , DOI: 10.26508/lsa.201900485
Peter Njenga Ng Ang A 1, 2, 3 , Julia K Ebner 1, 2, 3 , Matthias Plessner 1 , Klaus Aktories 1, 4 , Gudula Schmidt 5
Affiliation  

Engineering delivery systems for proteins and peptides into mammalian cells is an ongoing challenge for cell biological studies as well as for therapeutic approaches. Photorhabdus luminescens toxin complex (PTC) is a heterotrimeric protein complex able to deliver diverse protein toxins into mammalian cells. We engineered the syringe-like nanomachine for delivery of protein toxins from different species. In addition, we loaded the highly active copepod luciferase Metridia longa M-Luc7 for accurate quantification of injected molecules. We suggest that besides the probable size limitation, the charge of the cargo also influences the efficiency of packing and transport into mammalian cells. Our data show that the PTC constitutes a powerful system to inject recombinant proteins, peptides, and potentially, other molecules into mammalian cells. In addition, in contrast to other protein transporters based on pore formation, the closed, compact structure of the PTC may protect cargo from degradation.

中文翻译:

将发光杆菌毒素复合物 (PTC) 工程化至重组注射纳米机器中。

将蛋白质和肽引入哺乳动物细胞的工程递送系统对于细胞生物学研究以及治疗方法来说是一个持续的挑战。发光杆菌毒素复合物 (PTC) 是一种异三聚体蛋白质复合物,能够将多种蛋白质毒素输送到哺乳动物细胞中。我们设计了类似注射器的纳米机器,用于输送来自不同物种的蛋白质毒素。此外,我们还加载了高活性桡足类荧光素酶Metridia longa M-Luc7,以对注射分子进行准确定量。我们认为,除了可能的尺寸限制之外,货物的电荷也会影响包装和运输到哺乳动物细胞中的效率。我们的数据表明,PTC 构成了一个强大的系统,可以将重组蛋白、肽以及可能的其他分子注射到哺乳动物细胞中。此外,与其他基于孔形成的蛋白质转运蛋白相比,PTC 的封闭、紧凑结构可以保护货物免遭降解。
更新日期:2020-08-21
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